Late-Onset Aicardi-Goutières Syndrome: A Characterization of Presenting Clinical Features.
Late-Onset Aicardi-Goutières Syndrome: A Characterization of Presenting Clinical Features.
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晚期AICARDI-GOTIères综合征：呈现临床特征的表征。
DOI：
10.1016/j.pediatrneurol.2020.10.012
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发表时间：
2021-03
影响因子：
3.8
通讯作者：
Adang L
中科院分区：
文献类型：
--
作者：
Piccoli C;Bronner N;Gavazzi F;Dubbs H;De Simone M;De Giorgis V;Orcesi S;Fazzi E;Galli J;Masnada S;Tonduti D;Varesio C;Vanderver A;Vossough A;Adang L
古铁雷斯综合征（AGS）是一种遗传性干扰素病，其特征是早期发作的严重神经系统损伤伴颅内钙化、白质脑病和全身炎症。越来越多的神经功能障碍谱和表现超越婴儿期正在AGS中被认可。本研究的目的是表征晚婴儿和青少年发作的AGS。我们对1岁以上的AGS患者进行了一项多机构回顾性研究，包括病史、影像学特征和就诊时的疑似诊断。共鉴定出34个个体，均具有RNASEH 2B、SAMHD 1、ADAR 1或IFIH 1的致病性变异。大多数个体有发育迟缓和/或全身症状的病史，如不育性发热和冻疮，随后是与症状增加相关的前驱期。随后是突然发生的神经功能下降（暴发期），中位发病年龄为1.33岁（范围1.00-17.68岁）。大多数人表现出粗大运动技能的变化（97.0%），通常是音调增加（78.8%）。脑白质营养不良是最常见的MRI表现（40.0%）。钙化较少见（12.9%）。这是第一项研究，以表征介绍晚婴儿和青少年发作AGS及其表型谱。迟发性AGS可能表现为隐匿性，缺乏经典的临床和神经影像学表现。在暴发性疾病发作和运动症状消失之前，早期全身功能障碍的体征很常见。我们强烈建议在一岁以上的儿童中存在不明原因的持续炎症或运动技能变化时进行基因检测。
Aicardi Goutières Syndrome (AGS) is a genetic interferonopathy characterized by early onset of severe neurologic injury with intracranial calcifications, leukoencephalopathy, and systemic inflammation. Increasingly, a spectrum of neurologic dysfunction and presentation beyond the infantile period is being recognized in AGS. The aim of this study was to characterize late-infantile and juvenile onset AGS. We conducted a multi-institution, retrospective review of individuals with AGS who presented over 1 year old, including medical history, imaging characteristics and suspected diagnoses at presentation. Thirty-four individuals were identified, all with pathogenic variants in RNASEH2B, SAMHD1, ADAR1, or IFIH1. Most individuals had a history of developmental delay and/or systemic symptoms, such as sterile pyrexias and chilblains, followed by a prodromal period associated with increasing symptoms. This was followed by an abrupt onset of neurologic decline (fulminant phase), with a median onset at 1.33 years (range 1.00–17.68 years). Most individuals presented with a change in gross motor skills (97.0%), typically with increased tone (78.8%). Leukodystrophy was the most common MRI finding (40.0%). Calcifications were less common (12.9%). This is the first study to characterize presentation of late-infantile and juvenile onset AGS and its phenotypic spectrum. Late-onset AGS can present insidiously and lacks classic clinical and neuroimaging findings. Signs of early systemic dysfunction prior to fulminant disease onset and loss of motor symptoms were common. We strongly recommend genetic testing when there is concern for sustained inflammation of unknown origins or changes in motor skills in children more than one year of age.
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影响因子：
14.9
作者：
Orecchini E;Doria M;Antonioni A;Galardi S;Ciafrè SA;Frassinelli L;Mancone C;Montaldo C;Tripodi M;Michienzi A
通讯作者：
Michienzi A
影响因子：
3.8
作者：
Adang, Laura A.;Gavazzi, Francesco;Vanderver, Adeline
通讯作者：
Vanderver, Adeline
影响因子：
3.8
作者：
Tonduti, Davide;Izzo, Giana;Parazzini, Cecilia
通讯作者：
Parazzini, Cecilia
影响因子：
30.8
作者：
Rice GI;Del Toro Duany Y;Jenkinson EM;Forte GM;Anderson BH;Ariaudo G;Bader-Meunier B;Baildam EM;Battini R;Beresford MW;Casarano M;Chouchane M;Cimaz R;Collins AE;Cordeiro NJ;Dale RC;Davidson JE;De Waele L;Desguerre I;Faivre L;Fazzi E;Isidor B;Lagae L;Latchman AR;Lebon P;Li C;Livingston JH;Lourenço CM;Mancardi MM;Masurel-Paulet A;McInnes IB;Menezes MP;Mignot C;O'Sullivan J;Orcesi S;Picco PP;Riva E;Robinson RA;Rodriguez D;Salvatici E;Scott C;Szybowska M;Tolmie JL;Vanderver A;Vanhulle C;Vieira JP;Webb K;Whitney RN;Williams SG;Wolfe LA;Zuberi SM;Hur S;Crow YJ
通讯作者：
Crow YJ
影响因子：
5.3
作者：
Klok MD;Bakels HS;Postma NL;van Spaendonk RM;van der Knaap MS;Bugiani M
通讯作者：
Bugiani M